Alkaloid Croton Salutaris
2
Phytochemisfq.. 1981, Vol. 20. pp. 543-544. Pergamon Press Ltd. Printed in England. 0031-9422/81/030543-02 ~2.00/0 THE ALKALOIDS OF CROTON SALUTARIS RODERICKA. BARNES and ORLANDO M. SOEIRO Nlicleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941, RJ, Brazil (Received 24 June 1980) Key Word Index-Croton salutaris; Euphorbiaceae; salutarine; salutaridine; N-norsalutaridine. INTRODUCTION An earlier investigation [l ] led to the isolation of two alkaloids, salutarine and salutaridine, from the leaves and twigs of Croton salutaris Casar, a tree which is rather common in the mountains west of Rio de Janeiro at altitudes of about 2000m. The structure of salutaridine was finally established [2,3] by comparison with a sample prepared by Barton et al. [4] from phenolic dihydro- thebaine and confirmed by an X-ray study of its methiodide [5]. The present note deals with the nature of salutarine. RESULTS AND DISCUSSION The difference between salutarine and salutaridine was for a time elusive. The complete separation of the two was difficult and initial studies [2] of salutarine were made with a sample which still contained some salutaridine. A purification using initially the difference in the solubility of the picrates furnished pure salutarine which had no measurable optical rotation. However since the infra-red and magnetic resonance spectra were identical with those of salutaridine, salutarine must be the racemic form. The oriental plant Sirwmerzimt uc~rt~~ produces the levorotatory enantiomer [6,7]. Because the relative amounts of the two alkaloids were different in early collections, a more systematic observation was made during 1978. Plant material collected from the same area every other month was processed to separate the alkaloids and the optical rotation observed. For most of the year the rotation of the alkaloid mixture was 0 + 3”. However the mixture obtained in the colder months, May (+ 16”) and July (+ 8”), was definitely dextrorotatory indicating that salutaridine predominated. Barton et dl. [8] have observed a somewhat parallel seasonal variation in the incorporation of (+)-reticuline to form sinomenine in Sinomenium acutum. A possible explanation is that in Croton salutaris the cyclization which establishes the stereochemistry can take place either on an enzyme surface to form the benzylisoquinoline precursor to salutaridine or in solution to form a racemic precursor which leads to salutarine. TLC revealed the presence of small quantities of a third alkaloid. Fractions eluted from an alumina column after removal of most of the salutarine and salutaridine were combined and after prep. TLC the new alkaloid was isolated as an oil, readily oxidized in air. The MS and ‘H NMR spectrum showed that it was an alkaloid without the N-methyl group. The optical rotation of two samples of this alkaloid showed it to be N-norsalutaridine (l), containing different amounts of the racemic form. Me0 OH OMe I By analogy with Cfoton,flavens and C. linearis in which plants N-demethylation has been shown [9], our alkaloid could result from demethylation of both salutaridine and salutarine. However, this contrasts with the observation of Chambers et al. [lo] that C. balsamifera produces. salutaridine and N-norsinoacutine. The difference may be that the demethylating enzyme of C. salutaris is non specific while that of C. balsamifera effects reaction with only the levorotatory isomer. EXPERIMENTAL Salutarine. Leaves and twigs of Croton salutaris Casar, identified by Professor Paula Occhioni by comparison with a sample in the herbarium of the Botanical Garden, Rio de Janeiro, were extracted with alcohol and the bases separated with dil. HCI. The crude alkaloid mixture was treated with an equal weight of picric acid in EtOH. The picrate which separated, mp 222-7” after recrystallization proved to be that of salutaridine, mp 229-32”. Regeneration of the alkaloid from the picrate mother liquors, followed by chromatography on alumina (elution with benzene-EtOAc) and recrystallization from benzene-isopropanol furnished salutarine, mp 222-4” [a]P 0 + 0.5” (C,H,OH). ‘H NMR (lOOMHz, CDCI,): 2.45 (3H, s, NCH,), 3.75 (3H, s,OCH,), 3.88 (3H, s,OCH,),6.34 (lH, s, C-8). 6.72 (2H, AB pattern, C, + C,), 7.60 (lH, s, C-5). (Found: C, 69.38; H, 6.52; N, 4.2$ C,,H,,NO, requires: C, 69.70; H, 6.78; N, 4.18). The picrate of this alkaloid had mp 219-22” while a synthetic sample of ( f )-salutaridine (salutarine) prepared by Kametani and co-workers [1 ] was obtained as a yellow syrup which formed a picrate, mp 21 l-5”. N-norsalutaridine. The first sample of this base (1Omg) had [a]g + 80 f lo” (CIH50H) corresponding to about 70% norsalutaridine. A second sample showing a single spot on TLC 543
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Transcript of Alkaloid Croton Salutaris
Phytochemisfq.. 1981, Vol. 20. pp. 543-544. Pergamon Press Ltd. Printed in England. 0031-9422/81/030543-02 ~2.00/0
THE ALKALOIDS OF CROTON SALUTARIS
RODERICK A. BARNES and ORLANDO M. SOEIRO
Nlicleo de Pesquisas de Produtos Naturais, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941, RJ, Brazil
(Received 24 June 1980)
Key Word Index-Croton salutaris; Euphorbiaceae; salutarine; salutaridine; N-norsalutaridine.
INTRODUCTION
An earlier investigation [l ] led to the isolation of two alkaloids, salutarine and salutaridine, from the leaves and twigs of Croton salutaris Casar, a tree which is rather common in the mountains west of Rio de Janeiro at altitudes of about 2000m. The structure of salutaridine was finally established [2,3] by comparison with a sample prepared by Barton et al. [4] from phenolic dihydro- thebaine and confirmed by an X-ray study of its methiodide [5]. The present note deals with the nature of salutarine.
RESULTS AND DISCUSSION
The difference between salutarine and salutaridine was for a time elusive. The complete separation of the two was difficult and initial studies [2] of salutarine were made with a sample which still contained some salutaridine. A purification using initially the difference in the solubility of the picrates furnished pure salutarine which had no measurable optical rotation. However since the infra-red and magnetic resonance spectra were identical with those of salutaridine, salutarine must be the racemic form. The oriental plant Sirwmerzimt uc~rt~~ produces the levorotatory enantiomer [6,7].
Because the relative amounts of the two alkaloids were different in early collections, a more systematic observation was made during 1978. Plant material collected from the same area every other month was processed to separate the alkaloids and the optical rotation observed. For most of the year the rotation of the alkaloid mixture was 0 + 3”. However the mixture obtained in the colder months, May (+ 16”) and July (+ 8”), was definitely dextrorotatory indicating that salutaridine predominated. Barton et dl. [8] have observed a somewhat parallel seasonal variation in the incorporation of (+)-reticuline to form sinomenine in Sinomenium acutum. A possible explanation is that in Croton salutaris the cyclization which establishes the stereochemistry can take place either on an enzyme surface to form the benzylisoquinoline precursor to salutaridine or in solution to form a racemic precursor which leads to salutarine.
TLC revealed the presence of small quantities of a third alkaloid. Fractions eluted from an alumina column after removal of most of the salutarine and salutaridine were combined and after prep. TLC the new alkaloid was isolated as an oil, readily oxidized in air. The MS and ‘H NMR spectrum showed that it was an alkaloid without the N-methyl group.
The optical rotation of two samples of this alkaloid showed it to be N-norsalutaridine (l), containing different amounts of the racemic form.
Me0 OH OMe
I
By analogy with Cfoton,flavens and C. linearis in which plants N-demethylation has been shown [9], our alkaloid could result from demethylation of both salutaridine and salutarine. However, this contrasts with the observation of Chambers et al. [lo] that C. balsamifera produces. salutaridine and N-norsinoacutine. The difference may be that the demethylating enzyme of C. salutaris is non specific while that of C. balsamifera effects reaction with only the levorotatory isomer.
EXPERIMENTAL
Salutarine. Leaves and twigs of Croton salutaris Casar, identified by Professor Paula Occhioni by comparison with a sample in the herbarium of the Botanical Garden, Rio de Janeiro, were extracted with alcohol and the bases separated with dil. HCI. The crude alkaloid mixture was treated with an equal weight of picric acid in EtOH. The picrate which separated, mp 222-7” after recrystallization proved to be that of salutaridine, mp 229-32”. Regeneration of the alkaloid from the picrate mother liquors, followed by chromatography on alumina (elution with benzene-EtOAc) and recrystallization from benzene-isopropanol furnished salutarine, mp 222-4” [a]P 0 + 0.5” (C,H,OH). ‘H NMR (lOOMHz, CDCI,): 2.45 (3H, s, NCH,), 3.75 (3H, s,OCH,), 3.88 (3H, s,OCH,),6.34 (lH, s, C-8). 6.72 (2H, AB pattern, C, + C,), 7.60 (lH, s, C-5). (Found: C, 69.38; H, 6.52; N, 4.2$ C,,H,,NO, requires: C, 69.70; H, 6.78; N, 4.18). The picrate of this alkaloid had mp 219-22” while a synthetic sample of ( f )-salutaridine (salutarine) prepared by Kametani and co-workers [1 ] was obtained as a yellow syrup which formed a picrate, mp 21 l-5”.
N-norsalutaridine. The first sample of this base (1Omg) had [a]g + 80 f lo” (CIH50H) corresponding to about 70% norsalutaridine. A second sample showing a single spot on TLC
543
544 Short Reports
and having the correct “C NMR (being published separately) 3.
had [a]:& 589 578 546 nm
(c = 3.4). ‘H NMR 4.
+38.6 +40.8 +48.4 (lOOMHz, CDCI,): 3.78 (3H, s, OCH,), 3.92 (3H, s, OCH,), 6.32 5. (lH, s, C-8), 6.72 (2H, AB pattern, C-l + C-2), 7.58 (lH, s, C-5). 6. MS: M+ m/e 313.127 (36%) (C,,H,,NO, requires 313.131). 7.
Acknowledgements-The authors are indebted to the Ministry of 8. Planning (FINEP), The National Research Council (CNPq) and the Research Council of this University (CEPG) for financial 9. assistance. 10.
REFERENCES 11.
1. Barnes, R. A. and Gilbert, M. E. A. (1959) Bol. Inst. Quim. Agric. 58, 1.
2. Fong, J. W. (1962) Ph.D. Thesis, Rutgers University.
Barnes, R. A. (1964). An. Acad. Bras. CiBnc. 36, 238. Barton, D. H. R., Kirby, G. W., Steglich, W. and Thomas, G. M. (1963) Proc. Chem. Sot. 203. Collins, D. (1965) Ph.D. Thesis, Rutgers University. Hsu, J. S., Lo, S. Y. and Chu, J. H. (1964) Sci. Sinica 13,2016. Hsu, J. S., Lo, S. Y. and Chu, J. H. (1965) Chem Abstr. 62, 9183. Barton, D. H. R., Kirby, A. J. and Kirby, G. W. (1968) J. Chem. Sot. C, 929. Stuart, K. L. and Graham, L. (1971) J. C‘llmi. Sue. D, 392. Chambers, C., Haynes, L. J. and Stuart, K. L. (1966) Chem. Commun. 449. Kametani, T., Ihara, M., Fukumoto, K., and Yagi, H. (1969) J. Chem. Sot. C 2030.
